Synthesis and Biological Activity of C-6 and C-7 Modified Paclitaxels

✍ Scribed by Haiqing Yuan; Craig R Fairchild; Xian Liang; David G.I Kingston

• Publisher: Elsevier Science
• Year: 2000
• Tongue: French
• Weight: 160 KB
• Volume: 56
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(00)00611-6

✦ Synopsis

AbstractÐStructure modi®cation of paclitaxel at the C-6 and C-7 positions has been achieved using the readily available intermediate 6ahydroxy-7-epipaclitaxel (2). While a single diastereomer of the cyclic sul®te of 2 was prepared at lower temperature, both diastereomers were obtained at room temperature. The cyclic sulfate was found to be inert toward nucleophilic attack, which con®rms the great steric hindrance of the b-face of the C-6 and C-7 region of paclitaxel. Derivatization at the 6b-position with a nitrogen-containing function was accomplished using the alternate substrate 6a-tri¯uoromethanesulfonate ( 9), with the 7-epi hydroxyl group protected to avoid the formation of C-ring rearranged product. Hydrogenation of the 6b-azide was dif®cult but could be achieved in moderate yield under high pressure. Similar to other C-6 and C-7 modi®ed analogs reported earlier, these new compounds displayed comparable in vitro cytotoxicity to paclitaxel against the HCT116 human colon cancer cell line and the A2780 human breast cancer cell line.